Heterogeneity of antigen specificity between HLA-A*02:01 and other frequent Chinese HLA-A2 subtypes detected by a modified autologous lymphocyte-monocyte coculture. (October 2019)

• Record Type: Journal Article
• Authors: Chen, Jun; Lu, Shengjun; Weng, Xiufang; Liang, Zhihui; Wu, Xiongwen
• Is Part Of: Molecular immunology. Volume 114(2019:Oct.)
• Page Start: 389
• Page End: 394
• Publication Date: 2019-10
• Subjects: HLA-A2 -- Subtype -- Antigen specificity -- Coculture; Immunochemistry -- Periodicals; Molecular biology -- Periodicals; Immunochemistry -- Periodicals; Allergy and Immunology -- Periodicals; Molecular Biology -- Periodicals; Immunochimie -- Périodiques; Biologie moléculaire -- Périodiques; Immunochemistry; Molecular biology; Periodicals; Electronic journals; 571.96
• DOI: 10.1016/j.molimm.2019.08.014
• Languages: English
• ISSNs: 0161-5890

Abstract

Highlights: The heterogeneity in antigen specificity among HLA-A2 subtypes is low, and a given epitope formed by a single MHC molecule has a limited ability to promote lymphocyte proliferation. The relative proliferation frequency (RPF) is a sensitive and credible parameter for quantifying the heterogeneity in antigen specificity, which demonstrates the heterogeneity in antigen specificity of HLA-A2 subtypes. Modified autologous lymphocyte-monocyte co-culture method is a practical and reliable means to study the antigenicity of HLA allele subtypes in vitro . Abstract: HLA-A2 is the most common serological HLA type among all ethnic groups. Through advances in DNA typing, more than 800 subtypes of HLA-A2 have been identified, and the existence of heterogeneity of antigen specificity among the HLA-A2 subtypes has been suggested by retrospective analyses of allogeneic transplantation patients and by studies of antigen amino acid structure. However, prior to this study, the antigenicity of a given subtype or the mismatch extent between two given subtypes could not be studied in vitro. Here, we used a modified autologous lymphocyte-monocyte coculture method to reveal heterogeneity of antigen specificity among HLA-A2 subtypes. The coculture was set up with HLA-A2 (non-A*02:01) lymphocytes and monocytes, and the monocytes were coated with an HLA-A*02:01/IgG1-Fc fusion protein (dimer) by high-affinity binding of the IgG1-Fc to FcgRI. Lymphocyte proliferation following coculture indicated that HLA-A*02:01 showed antigenicity against the HLA-A2 (non-A*02:01) subtype. Among the most frequent HLA-A2 subtypes in the Chinese population (HLA-A*02:01, -A*02:03, -A*02:06 and -A*02:07), we identified significant -A*02:01 antigenicity for T cells from -A*02:03 or -A*02:06 but not -A*02:07 individuals. Our findings were consistent with retrospective studies of allograft patients with a limited number of involved subtypes, indicating that this modified coculture method provides a practical and reliable means to study the antigenicity of HLA allele subtypes in vitro.